Abstract
Hydroxy-alpha-sanshool, the active ingredient in plants of the prickly ash plant family, induces robust tingling paresthesia by activating a subset of somatosensory neurons. However, the subtypes and physiological function of sanshool-sensitive neurons remain unknown. Here we use the ex vivo skin-nerve preparation to examine the pattern and intensity with which the sensory terminals of cutaneous neurons respond to hydroxy-alpha-sanshool. We found that sanshool excites virtually all D-hair afferents, a distinct subset of ultrasensitive light-touch receptors in the skin and targets novel populations of Abeta and C fiber nerve afferents. Thus, sanshool provides a novel pharmacological tool for discriminating functional subtypes of cutaneous mechanoreceptors. The identification of sanshool-sensitive fibers represents an essential first step in identifying the cellular and molecular mechanisms underlying tingling paresthesia that accompanies peripheral neuropathy and injury.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Action Potentials / drug effects
-
Amides
-
Animals
-
Animals, Newborn
-
Capsaicin / pharmacology
-
Cells, Cultured
-
In Vitro Techniques
-
Isoquinolines / pharmacology
-
Mechanoreceptors / drug effects
-
Mechanoreceptors / physiology
-
Mice
-
Mice, Inbred C57BL
-
Mustard Plant
-
Nerve Fibers / drug effects
-
Nerve Fibers / physiology
-
Nerve Growth Factors / pharmacology
-
Neural Conduction / drug effects
-
Neural Conduction / physiology
-
Neurons, Afferent / drug effects
-
Neurons, Afferent / physiology*
-
Paresthesia / chemically induced*
-
Paresthesia / pathology*
-
Paresthesia / physiopathology
-
Plant Oils / pharmacology
-
Sensory Receptor Cells / drug effects
-
Sensory Receptor Cells / physiology
-
Sensory System Agents / pharmacology
-
Skin / innervation*
-
Statistics, Nonparametric
-
Touch / physiology
-
Trigeminal Ganglion / cytology
-
Urea / analogs & derivatives
-
Urea / pharmacology
-
gamma-Aminobutyric Acid / pharmacology
Substances
-
1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea
-
Amides
-
Isoquinolines
-
Nerve Growth Factors
-
Plant Oils
-
Sensory System Agents
-
sanshool
-
gamma-Aminobutyric Acid
-
Urea
-
neurotrophin 4
-
Capsaicin
-
mustard oil